The Chemical Biology Consortium is being developed by NCI's Division of Cancer Treatment and Diagnosis (DCTD), in conjunction with the Center for Cancer Research (CCR) and the NCI Office of the Director (OD) to facilitate the discovery and development of new agents to treat cancer. It is envisioned that initiation of this consortium will provide cutting-edge chemical tools for probing complex signaling pathways and will serve as the starting point for the elaboration of first-in-class targeted therapies. The CBC will be an integrated research consortium at the interface of chemical biology and molecular oncology that will, working with various programs within DCTD and CCR, establish an iterative cancer drug discovery group on the scale of a small biotechnology concern. The goal of the CBC will be to focus on unmet therapeutic needs in oncology that are not currently addressed by the private sector. The long-term vision of the CBC is to bridge the gap between basic scientific investigation and clinical research supported by the NCI as the first step in re-establishing the NCI as a world leader in the area of innovative cancer therapeutics discovery. To address this challenge and to ensure that NCI re-emerges as a strong and flexible player in the national cancer therapeutics discovery arena, we propose to develop a national effort in coordinated cancer drug discovery that unites academic and small biotechnology chemical biology and molecular oncology groups with the later-stage drug development resources of the NCI's Developmental Therapeutics Program (DTP). This unique effort will: 1. Focus on the identification of novel targets, and the development of new molecules to interrogate those targets and serve as lead structures around which potential drugs can be designed and tested by a restructured NCI therapeutics pipeline. This will be accomplished, in part, by establishing a consortium of chemists, chemical biologists, and molecular oncologists, formed in recognition of the increasing need for a highly interdisciplinary and creative team research effort in drug discovery, that will propel the NCI into the era of personalized therapeutic cancer medicine. These teams will be formed with funding through the use of NCI contracts, NCI-SAIC subcontracts, or NCI grants mechanisms, whichever is most expedient and appropriate to the scientific expertise required. 2. Establish an iterative drug discovery effort that will coalesce all segments of the current NCI therapeutics research activity, so that the development of promising chemical leads into bone fide clinical candidates can be accelerated 3. Build an enhanced, and robust drug pipeline with the goal of producing a new clinical agent for first-in-human clinical testing in the fourth quarter of 2009 The integrated process outlined here will allow NCI to maximize the return on its investment in molecular oncology over the past decade by consolidating and coordinating the essential chemical and biological technologies that are available and necessary for therapeutics development. This initiative will also streamline the therapeutics development workflow for chemists and biologists in academia and small business by enhancing the scientific infrastructure available to move their molecules along the entire drug development pipeline into first-in-human clinical trials. We believe that the NCI Chemical Biology Consortium will provide the new strategic approach that is required for NCI to re-establish itself as a world leader in anticancer drug discovery and development.